The proposed studies will extend the previous findings of this laboratory to expand our understanding of the metabolic and physiological relationships between the innervation of the cornea and the corneal epithelium. Previously developed quantitative, anatomical, and physiological methods for assessing structural and functional aspects of the sensory innervation will be applied to understanding the underlying causes of the well-known, but poorly understood decreased corneal sensitivity attributed to contact lens wear and to diabetes. Corneal sensitivity changes after contact lens wear will be studied in the rabbit. The object of this work will be to determine how contact lenses affect sensory transmission in the cornea. Rats made diabetic by injection of streptozotocin will be examined at various intervals by means of light and electron microscopy to determine the course of neural degeneration. Psychophysical studies of diabetic patients will correlate changes in corneal sensitivity with other neurological changes to determine if the cornea could provide a unique window into early sensory nerve changes in diabetics. Other studies will determine the fate of radiolabeled substances axoplasmically transported from the trigeminal ganglion to the corneal epithelium, and the routes by which these materials could become available to the epithelial cells. Nerve regeneration following penetrating keratoplasty will be examined to identify the barriers to restoration of the normal corneal neurology. It will be determined whether both high- and low-affinity systems exist for choline uptake in epithelial cells; also, the effects of specific denervation of the cornea and changes in epithelial mitotic activity, such as in wound healing, on the choline uptake system will be studied. Electrophysiological studies will permit the correlation of the anatomy and physiology of the corneal sensory receptors by intracellular recording from trigeminal ganglion cells, followed by the injection of an axoplasmically-transported tracer. Also, the sensory capabilities of wound-oriented collateral sprouts will be assessed in response to mechanical, thermal, and chemical stimulation. It may be that the types of changes seen in the parameters of the response characteristics will yield some insight into the mechanisms involved in the production of the abnormal sensations associated with corneal injury. Information from these studies could lead to the development of new therapeutic methods for accelerating corneal wound healing.